Evolving strategies in obstructive hypertrophic cardiomyopathy: myosin inhibitors as monotherapy compared with beta-blockers

Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by asymmetric hypertrophy, left ventricular outflow tract (LVOT) obstruction, and impaired diastolic function. β-adrenergic blockers (BB) have long been the cornerstone of medical therapy, providing symptomatic improvement but without disease-modifying effects. Cardiac myosin inhibitors (CMIs), including mavacamten and aficamten, represent a new therapeutic class targeting the hypercontractile sarcomere. Randomized trials have demonstrated substantial reductions in LVOT gradients and improvements in exercise capacity, New York Heart Association functional class, and quality of life, with an acceptable safety profile. Subgroup analyses from EXPLORER-HCM and FOREST-HCM suggested that concomitant BB therapy may blunt the exercise capacity benefits of CMIs. The MAPLE-HCM trial provided the first direct head-to-head comparison, showing that aficamten monotherapy was superior to metoprolol in improving peak oxygen uptake, functional status, and hemodynamic parameters. Current evidence indicates that CMIs offer greater efficacy than BB in improving exercise tolerance and LVOT obstruction in oHCM, supporting their role as potential first-line therapy. However, long-term safety, durability of benefit, optimal sequencing, and patient selection require further study. BBs remain clinically relevant for specific patient subgroups, but the advent of CMIs marks a paradigm shift from symptomatic relief toward targeted disease modification in oHCM.